Liquid handling device

ABSTRACT

A liquid handling device that determines a position of a tray utilizing light reflected from structural features of the tray.

BACKGROUND

Liquid handling devices may automatically deposit liquid into multiplewells of a well tray, such as a well plate. Misalignment of the welltray within the liquid handling device may result in misdeposition ofliquid into the well tray, such as no liquid deposited into some wells,too much liquid deposited into other wells, liquid depositedineffectively onto the interior walls of wells, and some liquiddeposited over the edge of the well tray. Moreover, these potentialproblems of well tray misalignment may be exacerbated when thedispensing location is desired to be near the perimeter boundary of thewell. Dispensing near the well perimeter is sometimes desired, forexample, when the dispenser is moving or when the dispenser comprisesmultiple dispensing nozzles that are located at different positions overa well. It may be desirable to reduce misdeposition of liquid into awell tray in a liquid handling device.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is schematic side view of one example embodiment of a liquidhandling device.

FIG. 2 is a top perspective view of one example embodiment of a specimentray of a liquid handling device.

FIG. 3 is one example embodiment of a reflected light signal reflectedfrom a specimen tray.

FIG. 4 is another example embodiment of a reflected light signalreflected from a specimen tray.

DETAILED DESCRIPTION OF THE DRAWINGS

FIG. 1 is schematic side view of one example embodiment of a liquidhandling device 10. Device 10 may be an automatic liquid handling (ALH)device including a housing 12 that includes therein a tray support 14adapted for supporting thereon a specimen tray 16, such as a well tray.Device 10 may further include a carriage 18 mounted on a carriage rod 20for movement across a width 22 (see FIG. 2) of tray 16 along a carriagerod axis 24. Tray support 14 may be adapted to move tray 16 in adirection 26, for example, though housing 12. Accordingly, movement oftray 16 in direction 26, and movement of carriage 18 along carriage rodaxis 24 may allow carriage 18 to be positioned above any region of tray16 as may be desired. Device 10 may further include a liquid depositiondevice 28, such as a printhead, that may be mounted on a second carriagerod 30 for movement along a second carriage rod axis 32. Accordingly,movement of tray 16 backwards and forwards in direction 26, and movementof deposition device 28 along second carriage rod axis 32 may allowdeposition device 28 to be positioned above any region of tray 16 as maybe desired.

In another embodiment, the specimen tray may be movable with respect tothe liquid dispensing device so as to allow positioning of thedispensing device above any region of the specimen tray as may bedesired.

Automated liquid handling device 10 may utilize specimen tray 16 toreceive small amounts of liquid automatically injected into each wellfrom deposition device 28. The specimen tray 16 may be utilized toperform capillary and nano liquid chromatography, genomic amplification,biological assays of experimental drug activity, or cell cultureapplications utilizing light microscopes, for example. The specimen tray16 may include several hundred, or thousands, of individual wells 34(some of which are shown in FIG. 2) that may have center-to-center welloffsets 35 (see FIG. 2) of 4.5 mm, or even 2.25 mm. Accordingly, evenslight misalignment of the specimen tray 16 on tray support 14, such asa rotation of less than 0.3 degrees about the z-axis 46, may result inpoor liquid dispensing. In other instances, much smaller rotations, forexample, as small as approximately 0.01 degrees, may result in poorliquid dispensing. This may happen under extreme instances, for example,when the center-to-center offsets of dispensing locations is as small asfilly microns and no accounting for misalignment is made. Poor liquiddispensing may include no liquid deposited into sonic wells, too muchliquid deposited into other wells, dispensing onto walls of wells, andsome liquid deposited over the edge of the well tray. In order to reducemisdeposition of liquid into specimen tray 16, Applicants' liquidhandling device 10 includes a tray position detection system 36.

Still referring to FIG. 1, tray position detection system 36 may behoused within carriage 18 and may include a light source 38, such as alight emitting diode (LED), and one or more light sensors 40 and 42. Inthe embodiment shown, first light sensor 40 is a spectral light sensorand second light sensor 42 is a diffuse light sensor. In otherembodiments, other light sources and/or sensors may be utilized, such asa monochromatic light sensor, a photo diode array, a CCD sensor, a CMOSsensor, an LED light source, a incandescent light source or a florescentlight source, for example. Light source 38 may be positioned at an angle44 of thirty degrees, for example, from a z-axis 46 perpendicular to xand y axes, 48 and 50 respectively, of specimen tray 16. Second lightsensor 42 may be positioned along perpendicular axis 46 and first lightsensor 40 may be positioned at an angle 52 of thirty degrees, forexample, from perpendicular axis 46. In other embodiments, other anglesmay be utilized for the source(s) and/or sensor(s) position as may bedesirable for a particular application. In use, a light beam 54 isprojected from light source 38 toward specimen tray 16 and the reflectedlight is sensed by sensors 40 and 42.

FIG. 2 is a top perspective view of one portion of an example embodimentof a specimen tray 16 of the liquid handling device 10 of FIG. 1.Specimen tray 16 may include structural features 64 such as a pluralityof individual wells 66, each including a well floor 68, one or more wellside walls 70 and ribs 72 positioned between each of adjacent individualwells 66. In the embodiment shown, ribs 72 may be defined as thehorizontal, upper surface of side walls 70. As light beam 54 (FIG. 1) isprojected to these structural features 64 of individual wells 66, thelight beam 54 may be reflected differently from different ones of thestructural features 64. The differences in the reflected light reflectedfrom these structural features 64 of the individual wells 66 may beutilized to determine the position and/or orientation of specimen tray16 within device 10.

Referring again to FIG. 1, in the example embodiment shown, spectralreflected light 56 that is reflected from structural features 64 of tray16 is detected by sensor 40 and diffuse reflected light 58 that isreflected from structural features of tray 16 is detected by sensor 42.The reflected light 56 and 58 detected by sensors 40 and 42,respectively, is then analyzed by a controller 60 connected to sensors40 and 42. Each of the reflected light signals received by controller 60may include information such as a signal peak height and/or a signalpeak location, that may correspond to or represent structural features64.

FIG. 3 is one example embodiment of a reflected spectral light signal 76of spectral reflected light 56 (FIG. 1) reflected from specimen tray 16.Controller 60 may analyze reflected spectral light signal 76 anddetermine that each of individual peaks 78 are spaced a distance apart80 of approximately 4.5 mm, for example. This spacing distance 80 maymatch the actual spacing distance of individual ribs 72 (see FIG. 2) ofspecimen tray 16. This measured peak spacing distance 80, therefore, maybe interpreted by controller 60 that the peaks 78 of reflected spectrallight signal 76 represent light reflected from each ribs 72 (see FIG.2). Accordingly, by determining a position of each of peaks 78,controller 60 may determine the position of each of ribs 72, and therebydetermine the position of specimen tray 16 on tray support 14. Utilizingthis positional information, controller 60 may direct liquid depositiondevice 28 to deposit liquid 82 (FIG. 1) out of individual orifices 84 ofdeposition device 28 and into individual ones of wells 66. Due to theknown location of the specimen tray 16 and individuals wells 66 therein,misdeposition of liquid 82 is reduced. In particular, instances of noliquid deposited into some wells 66, too much liquid 82 deposited intoother wells 66, dispensing onto the walls of wells, and some liquid 82deposited over an edge of the specimen tray 16, may be reduced or eveneliminated.

Referring again to FIG. 1, in one embodiment, carriage 18 may be movedacross specimen tray 16, during which time one or both of light sensors40 and 42 may sense a reflected light that is reflected from specimentray 16. In one example, light sensor 40 may sense a reflected spectrallight at locations spaced by a distance of at most 1/500th an inch, moreparticularly, may sense a reflected spectral light at locations spacedby a distance of approximately 1/600^(th) of an inch along specimen tray16. This may be accomplished by use of a linear encoder strip (notshown) positioned adjacent carriage 18. Carriage 18 may be moved alongcarriage rod 20 at a speed of approximately ten inches per second.Accordingly, in one embodiment, the signal 76 represented by FIG. 3 mayshow an intensity of reflected spectral light measured at every1/600^(th) of an inch across specimen tray 16, wherein some of themeasurements may record no measurable reflected light and may berepresented as a “zero” intensity reading shown between each of visiblepeaks 78.

FIG. 4 is one example embodiment of a reflected diffuse light signal 86,for example, of diffuse reflected light 58 reflected from specimen tray16. Controller 60 may analyze reflected diffuse light signal 86 todetermine that each of individual peaks 88 define a peak height 90,wherein the peak height 90 of each successive peak 88, as measured in adirection 92, steadily decreases. In other words, the peak intensity ofeach peak, as measured in direction 92, decreases. This pattern ofdecreased peak intensity may be interpreted by controller 60 that welltray 16 is spaced a close distance to light source 38 (see FIG. 1) in afirst edge region 94 (represented by the left region of FIG. 4) and thatwell tray 16 is spaced a further distance from light source 38 (seeFIG. 1) in a second edge region 96 (represented by the right region ofFIG. 4). Accordingly, controller 60 may determine that well tray 16 isrotated about the y axis 50 such that tray 16 is not positioned flat ontray support 14. Utilizing this positional information, controller 60may sound an alarm or provide an error message to an operator, or maydirect liquid deposition device 28 to deposit liquid 82 out ofindividual orifices 84 of deposition device 28 and into individual onesof wells 66 that are positioned within an appropriate liquid receivingrange from liquid deposition device 28.

Another interpretation of this pattern of decreasing peak height 90 orintensity, as measured in a direction 92, may be interpreted bycontroller 60 that well tray 16 is rotated about a z-axis such that thelight sensor is sensing less light reflected from a rib 72 because eachsuccessive rib may be positioned further from the light beam 54 of lightsource 38, as the sensor is moved in direction 92. The interpretation ofthe light sensed by the light sensors may be determined by multiplebaseline readings stored within controller 60 for a variety ofmisalignment situations.

In different embodiments of liquid handling device 10, spectral and/ordiffuse reflected light may be analyzed by controller 60. In oneembodiment wherein specimen tray 16 may be manufactured of a blackmaterial, reflected spectral light 56 may provide easily readable peaks78 (FIG. 3) for analysis by controller 60. In another embodiment whereinspecimen tray 16 may be manufactured or a clear material, reflecteddiffuse light 58 may provide easily, readable peaks 88 (FIG. 4) foranalysis by controller 60. Moreover, other variables, such as thedistance of the light source and/or sensors from the specimen tray, thetype, direction and/or intensity of the light projected to the specimentray, and the type of specimen tray, may also determine the analysisconducted by controller 60.

Determination of the positions of individuals wells 66 of specimen tray16 may allow a correction for specimen tray misalignment, may allowconfirmation of specimen tray format (the size, shape, and number ofwells), may allow calibration of a feed roller mechanism for drivingspecimen tray 16 through housing 12 (comparison of the specimen trayposition before and after movement), may allow for dispensing nearer thewell perimeter and from a greater number of nozzle positions, and mayallow for use of a lower cost feed roller mechanism due to the abilityto locate the specimen tray after positioning.

Given this capability to determine the positions of reflective featuresof a specimen tray, in another embodiment, it may also be beneficial toprovide specimen trays with reflective features 98, in addition towells, that are amenable to this reflective reading scheme. Thereflective features 98 may include a reflective material utilized tomanufacture the tray, and/or a reflective marking printed with areflective ink, such as a printed datum point 98, for example. Thesereflective features of a specimen tray may be used to align the trayand/or to identify it.

Other variations and modifications of the concepts described herein maybe utilized and fall within the scope of the claims below.

1. A liquid handling device, comprising: a tray support; a specimen traypositioned on said tray support, said specimen tray including structuralfeatures; a light source that directs a light toward said specimen tray;a light sensor that receives reflected light that is reflected from saidstructural features of said specimen tray; and a controller thatutilizes said reflected light to determine a position of said specimentray on said tray support.
 2. The device of claim 1 wherein saidspecimen tray comprises a well tray and said structural features includea plurality of wells each including a side wall and a floor.
 3. Thedevice of claim 1 wherein said light source comprises an LED and whereinsaid light sensor is chosen from at least one of a diffuse light sensorand a specular light sensor.
 4. The device of claim 1 wherein saidreflected light defines a light signal including peaks and wherein saidpeaks correspond to said structural features of said specimen tray. 5.The device of claim 1 further comprising a liquid deposition deviceincluding a plurality of deposition orifices, wherein individual ones ofsaid deposition orifices are controlled by said controller to depositliquid into said structural features of said specimen tray, based onsaid position of said specimen tray as determined by said controller. 6.The device of claim 1 further comprising a positioning device controlledby said controller to move said specimen tray into a controlled positionrelative to said light source.
 7. A method of manufacturing a liquidhandling device, comprising: positioning a tray on a tray support, saidtray including a plurality of liquid receiving structures; positioning alight source adjacent said tray such that a light beam projected fromsaid light source illuminates said liquid receiving structures; andpositioning a light sensor adjacent said tray such that a reflectedlight from said liquid receiving structures of said tray is received bysaid light sensor.
 8. The method of claim 7 further comprisingconnecting a controller to said light sensor wherein said controlleranalyzes said reflected light received by said light sensor to determinea position of said tray on said tray support.
 9. The method of claim 7further comprising positioning a second light sensor adjacent said traysuch that a second reflected light from said liquid receiving structuresof said tray is received by said second light sensor, and wherein saidlight sensor senses diffuse reflected light and said second light sensorsenses specular reflected light.
 10. The method of claim 8 furthercomprising positioning a liquid depositing device adjacent said tray,wherein said controller controls said liquid depositing device todeposit liquid into ones of said plurality of liquid receivingstructures based on said determined position of said tray on said traysupport.
 11. The method of claim 7 wherein said light source and saidlight sensor are positioned on a carriage that is movably positioned ona carriage rod for movement across said tray.
 13. A method of depositinga liquid into wells of a well tray, comprising: projecting a light towells of a well tray; sensing a reflected light that is reflected bysaid wells of said well tray; analyzing said reflected light todetermine a position of said wells of said well tray; and depositing aliquid into said wells of said well tray, wherein a location of saidliquid depositing is controlled based on said determined position ofsaid wells of said well tray.
 14. The method of claim 13 wherein saidanalyzing comprises at least one of analyzing a location of peaks of atleast one of a spectral reflected light signal and a diffuse reflectedlight signal and analyzing a height of peaks of at least one of aspectral reflected light signal and a diffuse reflected light signal.15. The method of claim 13 wherein said determining said position ofsaid wells includes determining a rotation of said well tray around anx-axis, a y-axis and a z-axis.
 16. The method of claim 13 wherein saidprojecting a light and said sensing a reflected light are each conductedat a plurality of locations along said well tray as said well tray ismoved relative to said a light projection device and a light sensingdevice.
 17. The method of claim 16 wherein said projecting a light andsaid sensing a reflected light are each conducted at a spacing of atmost 1/500ths of an inch across a width of said well tray.
 18. Themethod of claim 13 wherein said depositing a liquid into said wells ofsaid well tray includes depositing said liquid from a depositionstructure, and wherein controlling said location of said liquiddepositing comprises said controller selecting at least one nozzle froma multi-nozzle dispensing device and said controller controllingdispensing from said at least one nozzle.
 19. The method of claim 13further comprising: projecting a light to a reflective structure of awell tray; sensing a second reflected light that is reflected by saidreflective structure of said well tray; analyzing said second reflectedlight to determine a position of said reflective structure of said welltray; and wherein at least one of a location of said well tray and anidentification of said well tray is controlled based on said determinedposition of said reflective structure of said well tray.